Objective: Positron emission tomography (PET) using fluorine-18-fluoro-2-D-deoxyglucose (FDG) is increasingly being used to evaluate and manage oncology patients. Several reports have documented its utility in diagnosis, staging, response to treatment, and tumor viability assessment. There is, however, a paucity of literature on PET scanning in patients with osteosarcoma. We report results of serial F-18 FDG-PET scans in 16 untreated patients with osteosarcoma who underwent chemotherapy prior to surgical resection of the primary tumor site.Procedure: Changes in tumor fluoro-2-D-deoxyglucose (FDG) uptake were correlated with percent tumor necrosis on histopathology. PET studies were analyzed by visual assessment of tumor uptake of FDG by 3 independent observers, calculating a tumor to normal background activity ratio (TBR) by drawing regions of interest (ROIs) around the tumor and background activity in the contralateral normal limb, and percent change in TBR values between baseline and presurgical study.Results: All patients had positive baseline scans. Baseline TBRs ranged between 2.5-8.7 and visual assessment of intensity of FDG uptake was 2-3 on a scale of 0-3. At histopathologic examination, 8 patients were classified as good responses with more than 90% tumor necrosis and 8 patients as poor responses with less than 90% necrosis. Tumor necrosis was accurately predicted on PET scan in 15/16 patients by visual assessment, 14/15 patients by final TBR value on presurgery scans, and 7/15 patients using percent change of TBR on serial scans.Conclusions: The results of this small series suggest that FDG-PET scanning is fairly accurate in evaluating the response of osteosarcoma to chemotherapy. Visual assessment and TBR are more accurate in predicting tumor necrosis than percent change in TBR on serial scans.